Cancer is very difficult to cure after significant metastasis. Currently available treatments can prolong survival and improve quality of life in most metastatic cancers. This is achieved by using several treatment modalities either sequentially or in combination. Adding another novel therapeutic modality could potentially benefit millions of individuals fighting this disease.
Neoplastic cancer cells use glucose as the primary fuel to meet high energy demands. Cancer cells aggressively divert glucose from normal cells by up-regulating high affinity glucose transporters like Glucose Transporter 1 in the cell membrane.
Acquisition of the glycolytic phenotype has been shown to correlate with increased tumor aggressiveness and poor patient prognosis in several tumor types (Younes et al., 1995). Facilitative glucose uptake is achieved by trans-membrane transporters, termed Glut-1-5 and Glut-12, which are protein products of their respective GLUT genes. Although more than one Glut may be expressed by a particular cell type, tumors frequently over express Glut-1, which is a high affinity glucose transporter (Clavo et al., 1995). Human tumor cell lines, in response to hypoxia, increase glucose uptake by up-regulating membranous expression of the Glut-1 glucose transporter. This ability to survive periods of hypoxia confers tumors with an aggressive malignant phenotype enabling it to be resistant to both chemotherapy and radiotherapy and consequently poor overall survival. In several tumors including, NSCLC, colon cancer, bladder cancer, breast cancer and thyroid cancers, increased Glut-1 expression not only confers a malignant phenotype but also predicts for inferior survival (Younes et al., 1995; Younes et al. 1996a; Younes et al., 1996b).